LSU Health Sciences Center, Medical School, Stanley S. Scott Cancer Center, 533 Bolivar Street, New Orleans, LA 70112, USA.
Sbarro Institue for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA.
Genes (Basel). 2013 Mar 4;4(1):46-64. doi: 10.3390/genes4010046.
Glioblastoma multiforme is characterized by rapid proliferation, aggressive metastatic potential, and resistance to radio- and chemotherapy. The matricellular protein CYR61 regulates cellular proliferation and migration and is highly expressed in Glioblastomas. MicroRNAs are 22-nucleotides long RNAs that regulate gene expression post-transcriptionally. Here, we utilized the LN229 glioblastoma cell line and found that CYR61 is a target of miR-136, miR-155, and miR-634. Over-expression of miR-136 and miR-634 miRNAs negatively affected proliferation, but not migration, while expression of miR-155 reduced migration but did not affect the proliferation of LN229 cells. Investigation of the molecular mechanisms affected by expression of miR-634 revealed an increased phosphorylation of p70S6 kinase, suggesting an induction of the mammalian target of rapamycin (mTOR) complex 1 pathway. Additionally, in miR-634 overexpressing cells, TSC2, a negative regulator of mTOR signaling, was found to be decreased. Altogether, our study provides insights on the differential roles of miRs-136, -155, and -634 in regulating glioblastoma cell growth and migration, and how microRNAs could be manipulated to decrease the aggressiveness and metastatic potential of tumor cells.
多形性胶质母细胞瘤的特征是快速增殖、侵袭性转移潜能和对放化疗的耐药性。细胞基质蛋白 CYR61 调节细胞增殖和迁移，在胶质母细胞瘤中高度表达。 microRNA 是长 22 个核苷酸的 RNA，在后转录水平调节基因表达。在这里，我们利用 LN229 胶质母细胞瘤细胞系发现，CYR61 是 miR-136、miR-155 和 miR-634 的靶标。miR-136 和 miR-634 的过表达负调控增殖，但不影响迁移，而 miR-155 的表达降低迁移但不影响 LN229 细胞的增殖。对 miR-634 表达影响的分子机制的研究表明，p70S6 激酶的磷酸化增加，提示哺乳动物雷帕霉素靶蛋白（mTOR）复合物 1 途径的诱导。此外，在 miR-634 过表达的细胞中，mTOR 信号的负调节剂 TSC2 减少。总之，我们的研究提供了关于 miR-136、-155 和 -634 如何在调节胶质母细胞瘤细胞生长和迁移方面发挥不同作用的见解，以及如何操纵 microRNA 来降低肿瘤细胞的侵袭性和转移潜能。
